Prostate cancer is a heterogeneous disease progressing from prostatic intraepithelial neoplasia via locally invasive adenocarcinoma to hormone-refractory metastatic carcinoma (Demarzo et al., Lancet, 361:955, 2003). Prostate cancer develops most frequently in men over fifty, with more than 200,000 new cases diagnosed annually in the United States. Currently the second leading cause of cancer death in men is prostate cancer, exceeded only by lung cancer. It accounts for 29% of all male cancers and 11% of male cancer-related deaths.
Prostate cancer is typically diagnosed with a digital rectal exam and/or prostate specific antigen (PSA) screening (Schroder, Annal Oncol, 17(S10):201, 2006). An elevated serum PSA level is used as a marker for prostate cancer as only prostate cells secreted PSA. A healthy prostate will produce a stable amount, typically below 4 nanograms per milliliter, or a PSA level of 4 or less. Cancer cells on the other hand produce escalating amounts that correspond with the severity of the cancer. A level between 4 and 10 may raise a doctor's suspicion that a patient has prostate cancer, while amounts above 50 may show that the tumor has spread elsewhere in the body.
A major limitation of the serum PSA test is a lack of prostate cancer sensitivity and specificity especially in the intermediate range of PSA detection (4-10 ng/ml). Elevated serum PSA levels are often detected in patients with non-malignant conditions and provide little information about the aggressiveness of the cancer detected. Coincident with increased serum PSA testing, there has been a dramatic increase in the number of prostate needle biopsies performed (Jacobsen et al., JAMA, 274:1445, 1995), resulting in a surge of equivocal prostate needle biopsies (Epstein and Potter, J Urol, 166:402, 2001). Thus, development of additional serum and tissue biomarkers to supplement PSA screening is needed.
When initially diagnosed, prostate cancer in most patients is managed with either close observation in the absence of intervention (e.g., watchful waiting), surgical removal of the prostate (e.g., radical prostatectomy) or radiation involving the placement of radioactive pellets into the prostate (e.g., brachytherapy). However, for patients initially diagnosed with metastatic disease, it is already too late to perform brachytherapy or a radical prostatectomy. Therefore, these patients are typically treated initially with some type of testosterone suppressive therapy (Horwich, Annal Oncol, 17(S10):211, 2006). Once their cancer becomes hormone refractory, the median survival is 10-24 months.
Thus, additional methods that can be used for diagnosis and prognosis of prostate cancer are desirable. Moreover effective therapies for treating metastatic disease are needed. Accordingly, provided herein are methods that can be used in diagnosis and prognosis of prostate cancer. Further provided are methods that can be used to screen candidate bioactive agents for the ability to modulate signaling pathways in prostate cancer cells.